Congenital Coagulation Disorders (CCD) are inherited and present from birth. Their diagnosis depends on clinical awareness and correct laboratory investigations. The central registry for CCD or Congenital Bleeding Disorders (CBD) is at the Blood Services Centre, Kuala Lumpur Hospital and was established in 1975. There are 871 CCD registered. The commonest CCD are 631 (72%) Haemophilia A, 102 (12%) Haemophilia B and 93 (10.7%) von Willebrand's Disease. The other deficiencies registered are rare, only 45 in total:— Factor 1 (4), FV (4), FVII (21), FX (4), FXII (6), and FXIII (6). Diagnosis is based on clinical suspicion, screening tests namely the Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) and confirmation of the diagnosis was by doing specific factor assays. Molecular studies were done on FVIII and FXIII. Treatment is by transfusing the deficient factor when there is bleeding and comprehensive care involving the specialities like the neurologist/ neurosurgeon /orthopaedic / physiotherapy/ dental besides the haematologist and paediatrician to manage the complicatioons seen. There are fewer problems now as patients are diagnosed earlier and managed better. There is now a good prognosis and a better quality of life.
Analysis of the bleeding manifestations of 130 cases of dengue haemorrhagic fever admitted into the Children's ward of the General Hospital, Kuala Lumpur from May 1973 to September 1978 has been done. Petechial skin rash, epistaxis and gum bleeding were seen most commonly in mild and moderately severe cases. However, blood stained gastric aspirates, and severe haematemesis were seen in severe or very severe cases. Though with better vector control and preventive measures, a marked reduction in the incidence of the cases has been noted, severe cases were seen with symptoms of shock and gastrointestinal bleeding. These symptoms carried a bad prognosis. Among 15 children that died 10 had gastrointestinal bleeding and 2 had a disseminated intravascular coagulation defect. Lymphocytosis with atypical lymphocytes, low platelet count, low reticulocyte count and raised packed cell volume were the main haematological features seen in all these cases. All these features reverted to normal within a week. Mild evidence of disseminated intravascular coagulation was seen in a number of cases, but severe features were seen only in four. Two cases improved as a result of heparin therapy.
Virus associated haemophagocytic syndrome (VAHS), a distinct clinico-pathologic entity, is characterised by systemic proliferation of non-neoplastic histotiocytes showing haemophagocytosis resulting in blood cytopaenia. It has been described in relation to several viruses earlier. Here we describe a young girl who developed this reactive process during the course of dengue haemorrhagic fever (DHF).
We present three cases of Acquired Platelet Dysfunction with Eosinophilia (APDE). The importance of recognising this benign condition, which usually does not require any specific therapy, is stressed to avoid the pitfalls of diagnosing more serious bleeding disorders in children presenting with ecchymosis.
Four cases of Hb S were seen between Jan. 1976 and June 1976; three of them were newly discovered while the fourth was previously diagnosed. Out of the four cases, two were Malays and the other Indians. The family members of one Malay case were investigated. Six members had Hb S and three had Hb CoSp. Association of Hb CoSp and Hb S was seen in two of the members. Clinically they were healthy.
Hepatitis C virus (HCV) is the chief aetiologic agent for the parenterally transmitted Non-A, Non-B (NANB) hepatitis. This preliminary study was done to determine the prevalence of anti-HCV in the blood donor population. Blood from 3,540 donors who donated blood to the Blood Services Centre, Hospital, Kuala Lumpur, from 25th August 1991 to 13th January 1992, was tested for anti-HCV using both the Ortho and Abbott 2nd Generation ELISA test kits. ELISA positive specimens were repeated twice but no confirmatory test was done. There were 53 out of 3,540 (1.49%) blood donors who were repeatedly reactive to anti-HCV by ELISA. We plan to do further tests to confirm the results, using RIBA-2 or Abbott Neutralising test. Twenty eight out of 1,713 (1.63%) Malays, 22 out of 1,373 (1.60%) Chinese and 2 out of 393 (0.50%) Indians had antibodies to HCV. There was no significant difference in prevalence in the different age groups. The majority of donors tested were males (3,511 out of 3,540) of which 53 (1.50%) were anti-HCV positive. Only 29 females were tested and all were negative. To determine infectivity of the anti-HCV positive cases we would like to introduce testing for RNA by polymerate chain reaction (PCR). Screening all donated blood for anti-HCV will decrease, but not totally eliminate, post-transfusion hepatitis.
The hepatitis delta virus (HDV) is an RNA containing virus that requires hepatitis B virus (HBV) to supply the envelope proteins. HDV only infect man in the presence of HBV, either as a coinfection or as superinfection in HBV carriers. In the presence of hepatitis B infection, the HDV may cause more severe liver damage than that caused by the hepatitis B virus alone. HDV infection was studied in 44 HBsAg positive serum samples collected from male intravenous drug users sent for screening to the Blood Services Centre (BSC), Hospital Kuala Lumpur (HKL) between 1990 and 1992. The majority (39) were in the 20 to 39 age group. The youngest was 19 years old and the oldest was 61 years old. There were 25 Malays, 13 Chinese, five Indians and one Albanian. Anti hepatitis delta antibody (Anti-HDV) was detected in 15 out of 44 (34%) of the drug addicts. These results shows an increased in delta infection in HBsAg positive intravenous drug addicts compared to the surveillance results in 1985 when no delta antibodies were detected, and the 1986 and 1989 surveillance which showed 17.8% and 20% delta antibody positivity respectively.
Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.
The missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene 677C-->T is associated with modest elevation of homocysteine levels. The bio-ecogenetics factors of total homocysteine levels (tHcy) were investigated in a cross sectional study involving 53 randomly selected healthy Malay subjects. Results indicated that the prevalence of the homozygous 677T/T was 3.8% and heterozygous 677C/T was 17.0%. The levels of tHcy was higher in subjects aged more than 50 years (n = 7, 11.53 +/- 4.45 mumol/l) and in males (10.99 +/- 3.77 mumol/l) especially smoking males (12.19 +/- 3.62 mumol/l). THcy levels were low in the 3 pregnant subjects (4.44 mumol/l, p = 0.036) who were under folate supplementation.
Molecular analysis has been performed on a Malaysian patient with a severe bleeding disorder due to factor XIII(A) subunit deficiency. Total mRNA was isolated from the patient's leucocytes and four overlapping segments corresponding to the entire coding region of the A subunit cDNA were amplified by RT-PCR. The cDNA segments amplified efficiently and were of expected size. Direct sequencing of the complete reading frame revealed a single homozygous base change (nt 1327G-T) in exon 10 corresponding to a missense mutation, Val414Phe, in the catalytic core domain of the A subunit monomer. The mutation eliminates a BsaJ1 restriction site and family screening showed that both parents were heterozygous for the defect. The base substitution was absent in 55 normal individuals. Val414 is a highly conserved residue in the calcium-dependent transglutaminase enzyme family. Computer modelling based on 3D crystallographic data predicts that the bulky aromatic side chain of the substituted phenylalanine residue distorts protein folding and destabilizes the molecule. In addition, conformation changes in the adjacent catalytic and calcium binding regions of the A subunit are likely to impair the enzymatic activity of any protein synthesized.
Objective: This study was done to identify blood donors with thalassaemia and iron deficiency. A cross sectional study was carried out at Pusat Darah Negara (PDN), Kuala Lumpur in November 2003.
Methods: Full blood counts were done on 242 blood donors (166 males and 76 females) Hb analysis and serum ferritin assay were done for all the samples. The first time donors were used as controls.
Results: Only 20 (8.3%) donors had MCV <80 fL and MCH <26pg. Six of the 25 donors with iron deficiency had a low MCV <80 fL) and low MCH <26 pg) but all the 8 (40%) donors with thalassaemia or HbE had a low MCV and MCH! The mean ferritin levels were found to be lower among regular blood donors (95.3 ug/L) compared to first time blood donors (116.6 ug/L) but this was not statistically significant. There were 25 donors who were iron deficient: one was a first time donor and 24 were regular donors - 12 (50%) had donated 3 times a year in the last two years. Iron deficiency was seen in 12 Malays, and 9 Chinese, and 4 Indians. 13.3% of the males (22 out of 166 donors) and 4% (3 of 76) of female donors were iron deficient. Thalassaemia and HbE were found in 8 donors. HbE trait was identified in 5 Malay donors. One Malay and 1 Chinese donor had beta-thalassaemia trait. Another Chinese had alpha (a^o) thalassaemia trait. Neither HbE nor thalassaemia were seen in the Indian donors.
Conclusion: In this study thalassaemia and RbE were seen in 3.3% and iron deficiency in 10.3% of the 242 blood donors at PDN. Iron deficiency was present in 3.2% of the first time donors and 12.8% of the regular donors. Regular donors should have the serum ferritin done for their iron status and if their MCV and MCH are low, Hb analysis for thalassaemia or haemoglobinopathy.
Keywords: Blood donors, serum ferritin, iron deficiency, haemoglobinopathy